The skin contains various populaions of stem cells, but its characterization has been hampered by lack of markers and unclear location. The hair follicle has a niche for stem cells called a “bulge” which acts as a reservoir of multipotent stem cells. In the study reported here, an immunohistochemical and immunofluorescence analysis was performed on mouse and human tissues in order to determine the possible presence of stem cells of hair follicle through cytokeratin 15 (CK15), CD34, and CD200 markers identified as crucial to the stem cells and to identify the bulge region. Mouse (n = 7) and human (n = 7) skin samples were used. The expression of proteins was determined by the indirect immunoperoxidase technique and a secondary antibody bound to a fluorochrome. The specificity of staining was evaluated by negative controls. The results revealed that the stem cells associated with CD34 and CD200 antibodies were differentially expressed in the interfollicular epidermis, sebaceous glands, and bulge region, indicating that, in mice, CD34 and, in humans, CD200 are more specific than CK15 in detecting bulge cells. It also suggests that CD34 is specific for mouse bulge cells, while CD200 might have specificity for progenitor cells and partially differentiated cells in humans.
References
[1]
Owens, D.M. and Watt, F.M. (2003) Contribution of Stem Cells and Differentiated Cells to Epidermal Tumours. Nature Reviews Cancer, 3, 444-451.
https://doi.org/10.1038/nrc1096
[2]
Krause, K. and Foitzik, K. (2006) Biology of the Hair Follicle: The Basics. Seminars in Cutaneous Medicine and Surgery, 25, 2-10.
https://doi.org/10.1016/j.sder.2006.01.002
[3]
Schneider, M.R., Schmidt-Ullrich, R. and Paus, R. (2009) The Hair Follicle as a Dynamic Miniorgan. Current Biology, 19, R132-R142.
https://doi.org/10.1016/j.cub.2008.12.005
[4]
Dry, F.W. (1926) The Coat of the Mouse (Mus musculus). Journal of Genetics, 16, 287-340. https://doi.org/10.1007/BF02983004
[5]
Wang, H.-T., Chen, B., Tao, K., Tang, C.-W. and Hu, D.-H. (2007) Human Hair Follicle Bulge Cells: Potential Germ Cells for Skin Tissue Engineering. Journal of US-China Medical Science, 4, 1-8.
[6]
Voog, J. and Jones, L.D. (2011) Stem Cells and the Niche: A Dynamic Duo. Cell Stem Cell, 6, 103-115. https://doi.org/10.1016/j.stem.2010.01.011
Cotsarelis, G. (2006) Epihelial Stem Cells: A Folliculocentric View. Journal of Investigative Dermatology, 126, 1459-1468. https://doi.org/10.1038/sj.jid.5700376
[9]
Amoh, Y., Amoh, Y., Li, L., Katsuoka, K. and Hoffman, R.M. (2009) Multipotent Nestin-Expressing Hair Follicle Stem Cells. Journal of Dermatology, 36, 1-9.
https://doi.org/10.1111/j.1346-8138.2008.00578.x
[10]
Omary, M.B., Coulombe, P.A. and McLean, W.H.I. (2014) Intermediate Filament Proteins and Their Associated Diseases. The New England Journal of Medicine, 351, 2087-2100. https://doi.org/10.1056/NEJMra040319
[11]
Moll, R., Divo, M. and Langbein, L. (2008) The Human Keratins: Biology and Pathology. Histochemistry and Cell Biology, 129, 705-733.
https://doi.org/10.1007/s00418-008-0435-6
[12]
Lyle, S., Christofidou-Solomidou, M., Liu, Y., Elder, D.E., Albelda, S. and Cotsarelis, G. (1998) The C8/144B Monoclonal Antibody Recognizes Cytokeratin 15 and Defines the Location of Human Hair Follicle Stem Cells. Journal of cell Science, 111, 3179-3188.
[13]
Braun, K.M., Niemann, C., Jensen, U.B., Sundberg, J.P., Silva-Vargas, V. and Watt, F.M. (2003) Manipulation of Stem Cell Proliferation and Lineage Commitment: Visualisation of Label-Retaining Cells in Wholemounts of Mouse Epidermis. Development, 130, 5241-5255. https://doi.org/10.1242/dev.00703
[14]
Liu, Y., Lyle, S., Yang, Z. and Cotsarelis, G. (2003) Keratin 15 Promoter Targets Putative Epithelial Stem Cells in the Hair Follicle Bulge. The Journal of Investigative Dermatology, 121, 963-968. https://doi.org/10.1046/j.1523-1747.2003.12600.x
[15]
Ohyama, M., Terunuma, A., Tock, C.L., Radonovich, M.F., Pise-Masison, C.A., Hopping, S.B., Brady, J.N., Udey, M.C. and Vogel, J.C. (2006) Characterization and Isolation of Stem Cell-Enriched Human Hair Follicle Bulge Cells. The Journal of clinical Investigation, 116, 249-260. https://doi.org/10.1172/JCI26043
[16]
Krause, D.S., Ito, T., Fackler, M.J., Smith, O.M., Collector, M.I., Sharkis, S.J. and May, W.S. (1994) Characterization of Murine CD34, a Marker for Hematopoietic Progenitor and Stem Cells. Blood, 84, 691-701.
[17]
Simmons, D.L., Satterthwaite, A.B., Tenen, D.G. and Seed, B. (1992) Molecular cloning of a cDNA Encoding CD34, a Sialomucin of Human Hematopoietic Stem cells. Journal of Immunology, 148, 267-271.
[18]
Van de Rijn, M. and Rouse, R.V. (1994) CD34: A Review. Applied Immunohistochemistry, 2, 71-80.
[19]
Copland, D.A., Calder, C.J., Raveney, B.J., Nicholson, L.B., Phillips, J., Cherwinski, H.M., Jenmalm, M.C., Sedgwick, J.D. and Dick, A.D. (2007) Monoclonal Antibody-Mediated CD200 Receptor Signaling Suppresses Macrophage Activation and Tissue Damage in Experimental Autoimmune Uveoretinitis. The American Journal of Pathology, 171, 580-588. https://doi.org/10.2353/ajpath.2007.070272
[20]
Tiede, S., Kloepper, J.E., Bódó, E., Tiwari, S., Kruse, C. and Paus, R. (2007) Hair Follicle Stem Cells: Walking the Maze. European Journal of Cell Biology, 86, 355-376.
https://doi.org/10.1016/j.ejcb.2007.03.006
[21]
Trempus, C.S., Morris, R.J., Bortner, C.D., Cotsarelis, G., Faircloth, R.S., Reece, J.M. and Tennant, R.W. (2003) Enrichment for Living Murine Keratinocytes from the Hair Follicle Bulge with the Cell Surface Marker CD34. The Journal of Investigative Dermatology, 120, 501-511. https://doi.org/10.1046/j.1523-1747.2003.12088.x
[22]
Webb, A.N., Li, A. and Kaur, P. (2004) Location and Phenotype of Human Adult Keratinocyte Stem Cells of the Skin. Differentiation, 72, 387-395.
https://doi.org/10.1111/j.1432-0436.2004.07208005.x
[23]
Blanpain, C. and Fuchs, E. (2009) Epidermal Homeostasis: A Balancing Act of Stem Cells in the Skin. Nature Reviews Molecular Cell Biology, 10, 207-217.
https://doi.org/10.1038/nrm2636
[24]
Andl, T., Murchison, E.P., Liu, F., Zhang, Y.H., Yunta-Gonzalez, M., Tobias, J.W., Andl, C.D., Seykora, J.T., Hannon, G.J. and Millar, S.E. (2006) The miRNA-Processing Enzyme Dicer Is Essential for the Morphogenesis and Maintenance of Hair Follicles. Current Biology, 16, 1041-1049. https://doi.org/10.1016/j.cub.2006.04.005
[25]
Kloepper, J.E., Tiede, S., Brinckmann, J., Reinhardt, D.P., Meyer, W.M., Fässler, R. and Paus, R. (2008) Immunophenotyping of the Human Bulge Region: The Quest to Define Useful in Situ Markers for Human Epithelial Hair Follicle Stem Cells and Their Niche. Experimental Dermatology, 17, 592-609.
https://doi.org/10.1111/j.1600-0625.2008.00720.x
[26]
Jiang, S., Zhao, L., Purandare, B. and Hantash, B.M. (2010) Differential Expression of Stem Cell Markers in Human Follicular Bulge and Interfollicular Epidermal Compartments. Histochemistry and Cell Biology, 133, 455-465.
https://doi.org/10.1007/s00418-010-0684-z
[27]
Morrison, S.J. and Spradling, A.C. (2008) Stem Cells and Niches: Mechanisms That Promote Stem Cell Maintenance throughout Life. Cell, 132, 598-611.
https://doi.org/10.1016/j.cell.2008.01.038
[28]
Garcin, C.L., Ansell, D., Headon, D.J., Paus, R. and Hardman, M.J. (2016) Hair Follicle Bulge Stem Cells Appear Dispensable for the Acute Phase of Wound Re-Epithelialization. Stem Cells, 32, 1377-1385. https://doi.org/10.1002/stem.2289
[29]
Blanpain, C., Lowry, W.E., Geoghegan, A., Polak, L. and Fuchs, E. (2004) Self-Renewal, Multipotency, and the Existence of Two Cell Populations within an Epithelial Stem Cell Niche. Cell, 118, 635-648. https://doi.org/10.1016/j.cell.2004.08.012
[30]
Zhang, Y., Xiang, M., Wang, Y., Yan, J.J., Zeng, Y., Yu, J.H. and Yang, T. (2006) Bulge Cells of Human Hair Follicles: Segregation, Cultivation and Properties. Colloids and Surfaces B Biointerfaces, 47, 50-56.
https://doi.org/10.1016/j.colsurfb.2005.11.017
[31]
Inoue, K., Aoi, N., Sato, T., Yamauchi, Y., Suga, H., Eto, H., Kato, H., Araki, J. and Yoshimura, K. (2009) Differential Expression of stem-Cell-Associated Markers in Human Hair Follicle Epithelial Cells. Laboratory Investigation, 89, 844-856.
https://doi.org/10.1038/labinvest.2009.48
